Vaginal Microbiota Is Stable and Mainly Dominated by Lactobacillus at Third Trimester of Pregnancy and Active Childbirth: A Longitudinal Study of Ten Mexican Women.

In healthy women at reproductive age, the vaginal microbiota is mainly dominated by Lactobacillus bacteria during pregnancy and non-pregnancy stages. However, little is known about longitudinal changes within the vaginal microbiota composition from the third trimester of pregnancy to childbirth in healthy women. Thus, we conducted an exploratory longitudinal study of vaginal microbiota composition of 10 Mexican pregnant women, sampling from the same volunteer at two-time points: third trimester of pregnancy and active childbirth. Vaginal bacterial microbiota was characterized by V3-16S rDNA libraries by high-throughput sequencing and bioinformatics methods. Out of ten, vaginal microbiota from eight women was dominated by the Lactobacillus genus at both time points, whereas the other two women showed vaginal microbiota composition with high abundance of genera Gardnerella, Prevotella, and members of the Atopobiaceae family, without any preterm birth correlation. Importantly, we found no statistically significant differences in relative abundances, absolute reads count, alpha and beta diversity between the third trimester of pregnancy, and active childbirth time points. However, compared to the third trimester of pregnancy, we observed a trend with higher absolute reads counts for Gardnerella, Faecalibaculum, Ileibacterium, and Lactococcus genus at active childbirth and lower absolute reads count of Lactobacillus genus. Our results suggest that the vaginal microbiota composition is stable, and Lactobacillus genus is the dominant taxa in Mexican women's vagina at the third trimester of pregnancy and childbirth.

Probiotic lactobacilli in formulas and hygiene products for the health of the urogenital tract.

Lactobacilli are the predominant microorganisms of the healthy human vagina. A novel alternative for the prevention and treatment of female urogenital tract infections (UGTI) is the inclusion of these microorganisms as active pharmaceutical ingredients in probiotic formulas, and more recently in female hygienic products. Probiotics are defined as "live microorganisms that, when administered in adequate amounts, confer a health benefit on the host." A list of requirements must be considered during the development of probiotic product/formula for the female urogenital tract (UGT). This review aims to resume the requirements, probiotic characteristics, and clinical trial applied to determine the effect of probiotic and potentially probiotic strains on different woman's physiological and pathological conditions, and in preterm birth prevention. A revision of female hygienic products available in the world market is included, together with novel studies applying nanotechnology for Lactobacillus incorporation in hygienic products. Further studies and well-designed clinical trials are urgently required to complement the current knowledge and applications of probiotics in the female UGT. The use of probiotic formulas and products will improve and restore the ecological equilibrium of the UGT microbiome to prevent and treat UGTI in women under different conditions.

Colonization by multidrug-resistant microorganisms of hospitalized newborns and their mothers in the neonatal unit context.

INTRODUCTION: The mother plays a fundamental role in the constitution and regulation of her child's healthy microbiota, however, preterm newborns are separated from their mothers soon after birth and transferred to Neonatal Intensive Care Units, being exposed the constant risk for the development of multidrug-resistant microorganisms' infections. The aim of this study was to explore the multidrug-resistant microorganism colonization of hospitalized babies and their mothers in the neonatal unit context. METHODOLOGY: A prospective case study conducted with hospitalized babies and their mothers in the Neonatal Unit at a university hospital. The sample was composed of 433 binomials (mother-child). Colonization culture samples were taken at the moment of the baby's discharge, via two swabs in the oral, nasal, axillary, inguinal, and rectal regions. RESULTS: The colonization incidence among the binomials, 30 (6.9%) were both colonized by multi-resistant microorganisms. Mothers of colonized babies (24.4%) demonstrated a higher chance of colonization in comparison to mothers of non-colonized babies (11.9%) (p = 0.002). Relationships were drawn between baby colonization and prematurity, extremely low birth weight, and non-exclusive maternal breastfeeding (p<0.05). ESBL-producing Gram-negative microorganisms were more frequent in the cultures of the binomials, with 35.9% of the babies colonized with Klebsiella spp. ESBL and 42.0% of the mothers with Escherichia coli ESBL. Furthermore, 50% of the binomials were colonized with E. coli ESBL. CONCLUSION: The prematurity, extremely low birth weight, and non-exclusive breastfeeding at hospital discharge were associated with baby colonization by multidrug-resistant microorganism. Furthermore, mothers of colonized children presented higher chances of colonization.

Vaginal microbiome diversity and preterm birth: results of a nested case-control study in Peru.

PURPOSE: Preterm birth (PTB) is a major cause of neonatal mortality. The vaginal microbiome is associated with PTB, but results vary across racial/ethnic populations. Some evidence suggests gestational age affects this association. We investigated these associations in a novel population, conducting a post hoc analysis assessing if associations differed between women swabbed at different gestational ages. METHODS: We compared vaginal microbiomes from women with PTB (n = 25) to a random sample of women with term births (n = 100) among participants in the Pregnancy Outcomes, Maternal and Infant Study, conducted in Lima, Peru. Using DADA2, we identified taxa from 16S DNA sequencing and used Dirichlet multinomial mixture models to group into community state types (CSTs). RESULTS: If gestational age at sampling was not considered, no CST (diverse, Lactobacillus-dominated or Lactobacillus iners-dominated), was associated with PTB. Among women sampled before 12 weeks' gestation, women with Lactobacillus-dominated CSTs were less likely to have a PTB than those with a diverse CST. Among those swabbed between 12 and 16 weeks' gestation, the reverse was true. CONCLUSIONS: Our study supports previous literature suggesting that what constitutes a healthy vaginal microbiome varies by race/ethnicity. Longitudinal studies are necessary to disentangle effects of vaginal microbiome differences over gestation.

Periodontopathogenic microbiota, infectious mechanisms and preterm birth: analysis with structural equations (cohort-BRISA).

PURPOSE: The association between periodontopathogenic microbiota and preterm birth (PTB) has been overly studied. However, the biological mechanisms involved are little known. The objective is to evaluate the effect of periodontopathogenic bacteria burden (PBB), periodontal disease and other infections during pregnancy on preterm birth (PTB), through Structural Equation Modeling. METHODS: This was a case-control study nested in a prospective cohort called BRISA, including 330 pregnant women, 110 cases and 220 controls. This study included the following variables: cytokines interleukin-10 (IL-10) and transforming growth factor beta (TGF-ß), periodontal disease, PBB, age, socioeconomic status (SES), systemic infections and PTB. The correlations between variables were analyzed using Standardized Coefficient (SC). RESULTS: Greater PBB interfered positively with the occurrence of periodontal disease (SC: 0.027; p: 0.011), but these were not associated with the cytokines studied, nor with PTB. The lower serum levels of IL-10 (SC - 0.330; p 0.022) and TGF-ß (SC - 0.612; p < 0.001), and the presence of other systemic infections during pregnancy (SC 0.159; 0.049) explained the higher occurrence of PTB. CONCLUSION: It is possible that only the more severe periodontal disease and other systemic infections are capable of altering the cascade of cytokines regulating the inflammatory process and have an effect on the occurrence of PTB.

Preterm Birth, Inflammation and Infection: New Alternative Strategies for their Prevention.

BACKGROUND: Worldwide, the progress in reducing neonatal mortality has been very slow. The rate of preterm birth has increased over the last 20 years in low-income and middle-income countries. Its association with increased mortality and morbidity is based on experimental studies and neonatal outcomes from countries with socioeconomic differences, which have considered implementing alternative healthcare strategies to prevent and reduce preterm births. METHODS: Currently, there is no widely effective strategy to prevent preterm birth. Pharmacological therapies are directed at inhibiting myometrial contractions to prolong parturition. Some drugs, medicinal plants and microorganisms possess myorelaxant, anti-inflammatory and immunomodulatory properties that have proved useful in preventing preterm birth associated with inflammation and infection. RESULTS: This review focuses on the existing literature regarding the use of different drugs, medicinal plants, and microorganisms that show promising benefits for the prevention of preterm birth associated with inflammation and infection. New alternative strategies involving the use of PDE-4 inhibitors, medicinal plants and probiotics could have a great impact on improving prenatal and neonatal outcomes and give babies the best start in life, ensuring lifelong health benefits. CONCLUSION: Despite promising results from well-documented cases, only a small number of these alternative strategies have been studied in clinical trials. The development of new drugs and the use of medicinal plants and probiotics for the treatment and/or prevention of preterm birth is an area of growing interest due to their potential therapeutic benefits in the field of gynecology and obstetrics.

Polybacterial stimulation suggests discrete IL-6/IL-6R signaling in human fetal membranes: Potential implications on IL-6 bioactivity.

The polybacterial invasion of the amniotic cavity and risk of preterm birth is often due to cervicovaginal bacteria such as genital mycoplasmas (Mycoplasma hominis and Ureaplasma urealyticum) and Gardnerella vaginalis. The most studied biomarker associated with preterm birth is interleukin-6 (IL-6), a pleiotropic cytokine that performs different functions based on classical or trans-signaling mechanisms. This study evaluated the changes in IL-6 and IL-6 function associated accessory molecules by human fetal membranes to determine the functional availability of IL-6 assessment in an in vitro model of polybacterial infection. Fetal membranes were treated with LPS or heat-inactivated genital mycoplasmas and G. vaginalis alone or in combination. IL-6 and its soluble receptors (sgp130, sIL-6R) were assessed in conditioned medium by immunoassays and membrane-bound receptors were evaluated in the tissue using immunohistochemistry and RT-PCR. Data from protein and gene expression were evaluated using linear mixed effects models. Data from immunohistochemistry were evaluated using one-way analysis of variance followed by the Tukey test. Genital mycoplasmas alone, or in combination, inhibited IL-6 trans-signaling with increased sgp130 production. G. vaginalis activated the classical IL-6 signaling pathway, as did LPS. Polybacterial treatment resulted in a balanced response with neither pathway being favored. The increase in IL-6 production by fetal membranes in response to infection is likely a non-specific innate response and not an indicator of a functional mediator of any labor-inducing pathways. This suggests that correlating the risk of adverse pregnancy outcomes and designing interventions based on IL-6 levels without considering soluble receptors may be an ineffective strategy.

Shigellosis and Pregnancy in French Guiana: Obstetric and Neonatal Complications.

Shigella is a major cause of dysentery worldwide. Only a few cases of shigellosis during pregnancy have been reported. However, the neonatal and obstetric complications are potentially severe. The objective of this study was to describe the obstetric and neonatal complications of shigellosis during pregnancy. We carried out a retrospective study of 37 cases of shigellosis diagnosed in pregnant women at the maternity unit of Saint-Laurent du Maroni Hospital in west French Guiana between 2000 and 2014. Shigellosis diagnosis was based on the detection of Shigella in stool cultures from pregnant women (34 patients) or in a neonatal sample collected immediately after delivery (three neonates). In addition to the classic symptoms of shigellosis-an association of diarrhea, fever, and abdominal pain-we observed uterine contractions before the completion of 37 weeks of gestation in 61% of patients (N = 17/28). Cervical changes were associated with uterine contractions in 82% of cases (N = 14/17); 25% of the patients at risk of preterm birth went on to give birth prematurely (N = 3/12). Three cases of mother-to-child transmission were observed. Episodes of shigellosis in pregnant women may trigger uterine contractions and changes to the cervix, potentially resulting in miscarriage or preterm birth.

Maternal Chlamydia trachomatis Infections and Preterm Births in a University Hospital in Vitoria, Brazil.

BACKGROUND: Preterm birth (PTB) is a major determinant of neonatal morbimortality with adverse consequences for health. The causes are multifactorial, with intrauterine infection probably explaining most of these outcomes. It is believed that infection with Chlamydia trachomatis (CT) is also involved in PTB and premature rupture of membranes. OBJECTIVES: To evaluate the prevalence of and associated factors for CT among cases of PTB attended at a University Hospital in Vitoria, Brazil. METHODS: A cross-sectional study performed among parturient who had preterm birth from June 2012 to August 2013 in Vitoria, Brazil. Participants answered a questionnaire including demographic, behavioral, and clinical data. A sample of urine was collected and screened for CT using polymerase chain reaction. Chi-square tests were used for proportion differences and Student's-t tests and variance analysis were used for testing differences between mean values. Odds ratio was used as a measure of association with a 95% confidence interval. RESULTS: The prevalence of PTB during the period of the study was 26% and the prevalence of CT among them was 13.9%. A total of 31.6% pregnant women were younger than 25 years old and women infected by CT were even younger than women not infected by CT (p = 0.022). Most of them (76.2%) were married or had a living partner, and CT infection was more frequent among the single ones (p = 0.018); 16.7% of women reported their first sexual intercourse under 14 years old. The causes of prematurity were maternal-fetal in 40.9%; rupture of the membranes in 29.7% and premature labor in 29.4%. In multivariate analysis, being married was a protective factor for infection [OR = 0.48 (95%CI:0.24-0.97)]. None of the other characteristics were associated with CT infection. CONCLUSIONS: This study shows a high prevalence of CT infection among parturient who have preterm birth. This high prevalence highlight the need for defining screening strategies focused on young pregnant women in Brazil.

Preterm delivery and intimacy during pregnancy: interaction between oral, vaginal and intestinal microbiomes.

During pregnancy, the microbiomes of the mouth, vagina and intestine undergo changes to adapt to the demands of the body, increasing the relationship and similarity between them. Therefore, it is pertinent to consider a literature review to determine the existence of influencing factors for a specific microbiome, which could also modify others. An example is the case of the mouth microbiome that is dependent on the intimate activities of the female, and therefore could be a factor that relates to preterm labor.

Durante el embarazo los microbiomas bucal, vaginal e intestinal de la mujer sufren cambios para adaptarse a las demandas del cuerpo, aumentando la relación y similitud entre ellos. Debido a esto se considera pertinente realizar una revisión literaria con el propósito de determinar la existencia de factores que influyen en un microbioma específico y que posteriormente podrían modificar a los demás. Este es el caso del microbioma bucal que depende de la actividad íntima de la mujer y por consiguiente puede ser un factor que se relacione con el desarrollo de un embarazo pretérmino.

Microorganisms in the female genital tract during pregnancy: tolerance versus pathogenesis.

Microorganisms in the pregnant female genital tract are not always associated with pathology. The factors that influence the maternal response to microorganisms remain ill defined. We review the state of knowledge of microbe-host interactions in gestational tissues and highlight mechanisms that promote tolerance or pathogenesis. Tolerance to microorganisms is promoted during pregnancy by several mechanisms including upregulation of anti-inflammatory mediators, induction of endotoxin tolerance, and possibly by regulation of autophagy. Conversely, an altered vaginal microbiota or a pre-existing viral presence may result in induction of excessive inflammation and preterm labor. Although infections play a prevalent role in preterm birth, microbes are present in gestational tissues of women with healthy outcomes and may provide beneficial functions. The complex interactions between different microbial species and the maternal immune system during gestation remain incompletely elucidated.

[Maternal chorioamnionitis and neonatal conjunctive infection due to an infrequent pathogen]. / Corioamnionitis materna e infección conjuntival neonatal por un patógeno infrecuente.

Chorioamnionitis generates significant neonatal mortality and morbidity. Its incidence in premature birth can reach 30% and up to 30-40% of cases of premature rupture of membranes is due to this entity. We describe a case of chorioamnionitis by a commensal of the oral flora (Eikenella corrodens) in a pregnant woman with premature rupture of membranes and preterm delivery, which caused conjunctivitis in the newborn. On occasion of this case, we review the issue, delving into the diagnosis and clinical significance of this pathogen.

Correlates of cervical Mycoplasma genitalium and risk of preterm birth among Peruvian women.

BACKGROUND: Mycoplasma genitalium is associated with cervicitis and pelvic inflammatory disease in nonpregnant women. We investigated associations between cervical M genitalium, demographic and behavioral risk factors for sexually transmitted infection and preterm birth among low-income Peruvian women. METHODS: This case-control study, conducted at the Instituto Nacional Materno Perinatal, Lima, Peru, included 661 cases with a spontaneous preterm birth at <37 weeks and 667 controls who delivered at >or=37 weeks. Within 48 hours after delivery, subjects underwent interviews, medical record review, and collection of cervicovaginal specimens for M. genitalium, Chlamydia trachomatis, and Neisseria gonorrhoeae by nucleic acid amplification testing, and Trichomonas vaginalis by culture. Odds ratios and 95% confidence intervals were calculated for associations between M. genitalium, other genital infections and risk factors, and preterm birth. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: Cervical M. genitalium was detected in 3% of subjects and was significantly associated with C. trachomatis infection (P < 0.001) and preterm birth (4% vs. 2%; adjusted odds ratio: 2.5, 95% confidence interval: 1.2-5.0, P = 0.014), and marginally associated with T. vaginalis (P = 0.05). M. genitalium detection was also associated with younger maternal age (P = 0.003) but not with other risk factors for preterm birth. The association between cervical M. genitalium detection and preterm birth remained significant after adjustment for maternal age and coinfection with C. trachomatis or T. vaginalis. CONCLUSIONS: Cervical M. genitalium detection was independently associated with younger maternal age and preterm birth, suggesting that this organism may be an infectious correlate of spontaneous preterm birth.

Selective versus non-selective culture medium for group B streptococcus detection in pregnancies complicated by preterm labor or preterm-premature rupture of membranes

The objective of this study was to identify group B streptococcus (GBS) colonization rates and compare detection efficiency of selective versus non-selective culture media and anorectal versus vaginal cultures in women with preterm labor and preterm-premature rupture of membranes (PROM). A prospective cohort study of 203 women was performed. Two vaginal and two anorectal samples from each woman were collected using sterile swabs. Two swabs (one anorectal and one vaginal) were placed separately in Stuart transport media and cultured in blood-agar plates for 48 hours; the other two swabs were inoculated separately in Todd-Hewitt selective media for 24 hours and then subcultured in blood-agar plates. Final GBS identification was made by the CAMP test. A hundred thrity-two cultures out of 812 were positive. The maternal colonization rate was 27.6 percent. Colonization rates were 30 percent for preterm PROM and 25.2 percent for preterm labor. Todd-Hewitt selective medium detected 87.5 percent and non-selective medium 60.7 percent GBS-positive women. Vaginal samples and anorectal samples had the same detection rate of 80.3 percent. Anorectal selective cultures detected 75 percent of carriers; 39 percent of GBS-positive women were detected only in selective medium. A combined vaginal-anorectal selective culture is appropriate for GBS screening in this population, minimizing laboratory costs.

Selective versus non-selective culture medium for group B streptococcus detection in pregnancies complicated by preterm labor or preterm-premature rupture of membranes.

The objective of this study was to identify group B streptococcus (GBS) colonization rates and compare detection efficiency of selective versus non-selective culture media and anorectal versus vaginal cultures in women with preterm labor and preterm-premature rupture of membranes (PROM). A prospective cohort study of 203 women was performed. Two vaginal and two anorectal samples from each woman were collected using sterile swabs. Two swabs (one anorectal and one vaginal) were placed separately in Stuart transport media and cultured in blood-agar plates for 48 hours; the other two swabs were inoculated separately in Todd-Hewitt selective media for 24 hours and then subcultured in blood-agar plates. Final GBS identification was made by the CAMP test. A hundred thirty-two cultures out of 812 were positive. The maternal colonization rate was 27.6%. Colonization rates were 30% for preterm PROM and 25.2% for preterm labor. Todd-Hewitt selective medium detected 87.5% and non-selective medium 60.7% GBS-positive women. Vaginal samples and anorectal samples had the same detection rate of 80.3%. Anorectal selective cultures detected 75% of carriers; 39% of GBS-positive women were detected only in selective medium. A combined vaginal-anorectal selective culture is appropriate for GBS screening in this population, minimizing laboratory costs.